NMDA receptors in visual cortex are necessary for normal visuomotor integration and skill learning

Abstract

The experience of coupling between motor output and visual feedback is necessary for the development of visuomotor skills and shapes visuomotor integration in visual cortex. Whether these experience dependent changes of responses in V1 depend on modifications of the local circuit or are the consequence of circuit changes outside of V1 remains unclear. Here, we probed the role of NMDA receptor dependent signaling, which is known to be involved in neuronal plasticity, in mouse primary visual cortex (V1) during visuomotor development. We used a local knockout of NMDA receptors and a photoactivatable inhibition of CaMKII in V1 during first visual experience to probe for changes in neuronal activity in V1 as well as the influence on performance in a visuomotor task. We found that a knockout of NMDA receptors before, but not after, first visuomotor experience reduced responses to unpredictable stimuli, diminished the suppression of predictable feedback in V1, and impaired visuomotor skill learning later in life. Our results demonstrate that NMDA receptor dependent signaling in V1 is critical during first visuomotor experience for shaping visuomotor integration and enabling visuomotor skill learning.

The locus coeruleus broadcasts prediction errors across the cortex to promote sensorimotor plasticity

“…One plausible function of LC sensorimotor prediction errors is to gate the plasticity that underlies learning of sensorimotor predictions, e.g., the prediction of visual feedback during locomotion. Primary sensory cortices can indeed learn to suppress the sensory consequences of locomotion, driving selective reductions of responses to locomotion-coupled inputs (Schneider et al, 2018; Widmer et al, 2022).…”

“…If this interpretation is correct, then extensive training within the VR should also lead to visual flow response suppression during locomotion even in mice without artificial LC axon stimulation. To assess this idea, we reanalyzed two-photon calcium imaging data from V1 layer 2/3 in coupled trained mice reared with visual experience entirely constrained to that of the visuomotor coupling in the VR across days (and otherwise dark reared) (Attinger et al, 2017; Widmer et al, 2022) ( Figure 5A ). We compared this data to similar data from normally reared mice that also have experience of the virtual reality system, but that had experience of normal visuomotor coupling in freely moving conditions (Vasilevskaya et al, 2022; Zmarz and Keller, 2016) ( Figure 5A ).…”

“…In the primary visual cortex (V1), excitatory neurons in layer 2/3 compute mismatches between visual flow speed and locomotion speed (Attinger et al, 2017; Jordan and Keller, 2020; Keller et al, 2012; Zmarz and Keller, 2016). Such sensorimotor prediction error responses in the cortex depend on ongoing and developmental experience with sensorimotor coupling (Attinger et al, 2017; Schneider et al, 2018; Vasilevskaya et al, 2022; Widmer et al, 2022), and therefore the computation underlying them is actively learned. In predictive processing, one main function of prediction errors is to drive corrective plasticity in the internal model that generates predictions (Keller and Mrsic-Flogel, 2018).…”

Functional correlates of immediate early gene expression in mouse visual cortex

“…During first visuomotor exposure in life, experience with coupling between movement and visual feedback is thought to coordination inputs onto layer 2/3 neurons in primary visual cortex (V1) such that individual neurons receive balanced and opposing top-down motor-related and bottom-up visual input (Attinger et al, 2017;Leinweber et al, 2017;Jordan & Keller, 2020). While visual input without visuomotor coupling is sufficient to establish normal visual responses in layer 2/3 neurons, the emergence of visuomotor mismatch responses is contingent on experience with visuomotor coupling (Attinger et al, 2017) and relies on NMDA receptor dependent signaling in the local V1 circuit (Widmer et al, 2022). How top-down and bottom-up inputs are coordinated during visual and visuomotor experience and whether plasticity mechanisms in the bottom-up visual driven pathway are the same as those engaged in the topdown motor-related input is still unclear.…”

Functional correlates of immediate early gene expression in mouse visual cortex

“…During first visuomotor exposure in life, experience with coupling between movement and visual feedback is thought to coordination inputs onto layer 2/3 neurons in primary visual cortex (V1) such that individual neurons receive balanced and opposing top-down motor-related and bottom-up visual input (Attinger et al, 2017; Jordan and Keller, 2020; Leinweber et al, 2017). While visual input without visuomotor coupling is sufficient to establish normal visual responses in layer 2/3 neurons, the emergence of visuomotor mismatch responses is contingent on experience with visuomotor coupling (Attinger et al, 2017) and relies on NMDA receptor dependent signaling in the local V1 circuit (Widmer et al, 2022). How top-down and bottom-up inputs are coordinated during visual and visuomotor experience and whether plasticity mechanisms in the bottom-up visual driven pathway are the same as those engaged in the top-down motor-related input is still unclear.…”